Lauri A Aaltonen1. 1. Tumor Genomics Group, Academy of Finland and Genome-Scale Biology Research Program/Biomedicum, Department of Medical Genetics, University of Helsinki, Helsinki, Finland. lauri.aaltonen@helsinki.fi
Abstract
BACKGROUND: Recently, researchers at the Oulu University Hospital and the University of Helsinki identified a large pedigree segregating prolactinomas and somatotropinomas. Results suggest that this family from Northern Finland has a possible low penetrance of hereditary predisposition to development of pituitary adenoma, and in particular growth hormone-secreting tumors. We applied cancer genetics tools such as genomic and expression arrays to identify the gene responsible for the tumors identified in this kindred and found that the same ancestral founding mutation caused the disease. Review of population-based data showed that approximately 45 individuals were diagnosed with acromegaly in this area of Finland within a limited time frame. Of those individuals, 16% were positive for a mutation of the aryl hydrocarbon receptor-interacting protein (AIP) mutation. We proposed using the term pituitary adenoma predisposition (PAP) to describe a person with an AIP germline mutation. Tumor immunohistochemistry testing can be used for subjects with a reasonable suspicion of PAP to determine whether the tumor is negative for the AIP protein. If so, the subject can be referred for genetic counseling and then can decide whether to undergo genetic testing. CONCLUSIONS: Further study is needed to further define the PAP syndrome, delineate its phenotype and determine whether there is some component tumor associated with it. Functional work on AIP should shed new light on the mechanisms of pituitary tumorigenesis. Copyright (c) 2007 S. Karger AG, Basel.
BACKGROUND: Recently, researchers at the Oulu University Hospital and the University of Helsinki identified a large pedigree segregating prolactinomas and somatotropinomas. Results suggest that this family from Northern Finland has a possible low penetrance of hereditary predisposition to development of pituitary adenoma, and in particular growth hormone-secreting tumors. We applied cancer genetics tools such as genomic and expression arrays to identify the gene responsible for the tumors identified in this kindred and found that the same ancestral founding mutation caused the disease. Review of population-based data showed that approximately 45 individuals were diagnosed with acromegaly in this area of Finland within a limited time frame. Of those individuals, 16% were positive for a mutation of the aryl hydrocarbon receptor-interacting protein (AIP) mutation. We proposed using the term pituitary adenoma predisposition (PAP) to describe a person with an AIP germline mutation. Tumor immunohistochemistry testing can be used for subjects with a reasonable suspicion of PAP to determine whether the tumor is negative for the AIP protein. If so, the subject can be referred for genetic counseling and then can decide whether to undergo genetic testing. CONCLUSIONS: Further study is needed to further define the PAP syndrome, delineate its phenotype and determine whether there is some component tumor associated with it. Functional work on AIP should shed new light on the mechanisms of pituitary tumorigenesis. Copyright (c) 2007 S. Karger AG, Basel.
Authors: G Occhi; M L Jaffrain-Rea; G Trivellin; N Albiger; F Ceccato; E De Menis; M Angelini; S Ferasin; A Beckers; F Mantero; C Scaroni Journal: J Endocrinol Invest Date: 2010-03-30 Impact factor: 4.256